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RIDC Redoxoma


How the molecules that make our skin sense sunlight work

And why moderate sun exposure without protection is good for health
PorBy Maria Celia Wider
• CEPIDRIDC Redoxoma
05/04/2021
São Paulo, Braszil

The skin, the largest organ in the human body, is also a light-detecting organ, with a photosensitive system similar to that of the eye. When we expose ourselves to the sun, our skin receives not only the dreaded ultraviolet radiation but also visible light and infrared radiation. We receive billions of photons, which interact with molecules that absorb light in the skin, such as biomolecules, endogenous chromophores, pigments, and opsins. The beneficial or harmful effects of exposure to the sun depend on these interactions.

“Our skin cells have molecules that were selected in biological evolution to feel the light, we have many pigments in the skin that absorb light. The photons themselves are not mutagenic, they do nothing unless they are absorbed - then they participate in photochemical reactions, generating molecules in excited states, which react chemically with other molecules”, explains professor Mauricio S. Baptista, from the Instituto de Química at Universidade de São Paulo (USP) and a member of the RIDC Redoxoma.

Among the molecules that capture light, opsins are proteins that modulate many of the cellular responses to sun exposure and can be considered as ’the eyes of the skin’. “Opsins, in reality, are receptors that have a chromophore, that is, a portion where the physical-chemical interactions with light energy occur, causing a change in the conformation of the entire molecule. As it is a membrane protein, when it changes the conformation it starts to interact with other intracellular proteins and triggers a cascade of reactions, provoking a biological response ”, says professor Ana Maria de Lauro Castrucci, from the Instituto de Biociências at USP and the University of Virginia.

The Baptista and Castrucci groups published the review article How does the skin sense sun light? An integrative view of light sensing molecules, in the Journal of Photochemistry & Photobiology, C: Photochemistry Reviews, with the goal to provide a global analysis of how the skin detects light of different wavelengths through interactions with chromophores and opsins.

Opsins

Skin cells, such as keratinocytes, fibroblasts, and melanocytes, can detect the presence of sunlight using a set of proteins called opsins. However, this was unknown until the year 2000, as only vision opsins, present in the retina - the rhodopsin and cone opsins for color vision - were known. At that time it was already known that the blind person continued to have biological rhythms adjusted to the light/dark cycle, but, in experiments with animals, it was found that, if the eyes were removed, this adjustment was lost. The molecules responsible for this remained to be discovered. It was then that, “using as a model the African frog Xenopus laevis, whose skin changes color with the light, American scientists isolated a new opsin, which they called melanopsin because it was found in melanophores. Melanopsin, present in the retina of all vertebrates, is responsible for the perception of light/dark, without forming an image,” says Professor Castrucci, who was doing a senior internship in the laboratory of researcher Ignacio Provencio, where the discovery was made, and since then works with these photopigments.

In addition to adjusting the circadian rhythm, these opsins are associated with the pupillary reflex, which controls the diameter of the pupils in response to the intensity of the light; and the decrease in melatonin production by exposure to light - that’s why you shouldn’t have a light on in your room at night, or television on. Melanopsin is known to be more sensitive to the wavelength corresponding to the blue color.

Investigating the properties of melanopsin, Castrucci’s group found that these opsins also act as a thermosensor and they are present in “blind tissues”, such as white and brown adipose tissue, and in internal organs, such as the heart. The researcher believes that they may have a role as temperature and metabolite sensors.

Since the discovery of melanopsins in the skin of frogs, several other types of opsins have been found in the skin cells of several animals, including mammals. In humans, a wide variety of opsins is expressed in different types of skin cells, including keratinocytes, melanocytes, fibroblasts, and hair follicle cells. “Over the past 20 years, there has been a tremendous evolution in the discovery of other opsins present not only in the Central Nervous System but also in the skin of mammals,” says the researcher.

Although these opsins are responsible for the detection of light in the skin, their biological functions are not entirely elucidated. For now, studies have shown that they modulate various physiological processes in the skin, including wound healing, melanogenesis, photoaging, and hair growth. And, according to the researchers, they may be responsible for the benefits of sun exposure.

Sun: friend or foe?

The sun emits a broad spectrum of electromagnetic radiation, which includes gamma rays, ultraviolet radiation, visible light, and infrared radiation. Much of this radiation does not reach the Earth’s surface, which is protected mainly by its magnetic field and the ozone layer. The ozone layer absorbs radiation below 280 nanometers, which means that only ultraviolet A and B radiation (UVA and UVB), visible and infrared radiation come into contact with the human skin.

Image by Scientific Committee on Emerging and Newly Identified Health Risk under Creative Commons
Image by Scientific Committee on Emerging and Newly Identified Health Risk (Health Effects of Artificial Light, Report, 2012) http://dx.doi.org/10.2772/8624 under Creative Commons

Baptista explains that, shortly after the absorption of a photon by a molecule in the fundamental state, an excited state is formed, which is much more reactive than its respective fundamental state. The damage mechanisms induced by solar radiation are mainly due to this photosensitization, a process by which molecules transform light energy into chemical reactivity.

Spending excessive periods of time in the sun is detrimental to the skin and overall health. Molecules in our DNA absorb UVB photons, generating a photochemical reaction that results in DNA damage. The acute effect of these DNA changes is a strong inflammatory response also known as sunburn, in which the skin becomes reddish and painful to touch. When DNA damage is not repaired, mutations occur that can lead to the development of cancer.

Therefore, photoprotection strategies focus mainly on avoiding exposure to UV rays. However, according to the researchers, these strategies are misguided, because this radiation comprises only about 2% of the solar radiation that reaches the Earth’s surface. Most of the photons that reach us are in the visible, about 47%, and in the infrared range, about 51%. “It is undeniable that a person who sunbathes on the beach and is correctly using commercially available sunscreen will not be protected against 98% of the photons that will come in contact with her skin”.

And not just UV radiation is dangerous. Photons in the visible and infrared bands penetrate the skin much deeper than UV rays, generate reactive oxidants, and can saturate the skin’s redox defenses. When we expose ourselves to the sun using sunscreen, we get tanned. This is due to the production of melanin by melanocytes, cells located in the barrier between the epidermis and the dermis that perceive blue light and UVA radiation through opsins. Melanin is a pigment responsible for skin color and protection against UVB rays. However, induced by visible light and UVA radiation, it can also cause oxidative stress and indirect DNA damage, as has already been demonstrated by Baptista’s group.

But sunbathing also has many beneficial health effects. The best known is the synthesis of vitamin D: approximately 90% of all vitamin D used in our body is formed by the action of UVB rays on the skin. Vitamin D plays an important role in regulating the levels of calcium and phosphorus in our body, improving bone and muscle health, strengthening the immune system, and preventing various types of cancer, cardiovascular diseases, depression, and other diseases.

Also, we use sunlight to adjust our central biological clock, and interruptions in this rhythm can have negative health effects. Low exposure to the sun can also aggravate conditions such as obesity and cardiovascular disease. Another important benefit of sun exposure was shown in an English study, according to which 20 minutes of sun exposure can lower blood pressure for hours. The explanation is that solar radiation activates the production of nitric oxide, a potent vasodilator, which lowers blood pressure. This may explain the higher incidence of cardiovascular disease at higher latitudes than in the tropics. Another study evaluated nearly 30,000 women over 20 years in Sweden and showed that women who regularly exposed themselves to the sun lived up to two years longer than those who did not receive much sunlight.

Considering this evidence, the researchers highlight the urgent need for a new paradigm of photoprotection, which considers the benefits for the well-being and human health of moderate sunbathing with no sunscreen. Estimates of how long is a “moderate exposure” vary. According to the authors, population studies show that people with fair skin, in temperate regions, should spend about 10 to 20 minutes sunbathing, three times a week, with the whole body exposed - with no sunscreen. People with darker skin tones, that is, those who produce more melanin, can spend more time in the sun without noticeable acute effects of radiation on the skin, but they are not safe from chronic effects, so they should also follow the recommendation to sunbathe without protection for a limited time.

The article How does the skin sense sun light? An integrative view of light sensing molecules, by Leonardo Vinicius Monteiro de Assis, Paulo Newton Tonolli, Maria Nathalia Moraes, Maurício S. Baptista and Ana Maria de Lauro Castrucci, can be accessed here.